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A panel of national experts was convened by the Infectious Diseases Society of America (IDSA) to update the
2005 guidelines for the treatment of skin and soft tissue infections (SSTIs). The panels recommendations were
developed to be concordant with the recently published IDSA guidelines for the treatment of methicillin-
resistant Staphylococcus aureus infections. The focus of this guideline is the diagnosis and appropriate treatment
of diverse SSTIs ranging from minor supercial infections to life-threatening infections such as necrotizing fas-
ciitis. In addition, because of an increasing number of immunocompromised hosts worldwide, the guideline
addresses the wide array of SSTIs that occur in this population. These guidelines emphasize the importance
of clinical skills in promptly diagnosing SSTIs, identifying the pathogen, and administering effective treatments
in a timely fashion.
recommended to help identify whether Staphylococcus aureus (b) Oral therapy for ecthyma or impetigo should be a 7-day
and/or a -hemolytic Streptococcus is the cause (strong, moder- regimen with an agent active against S. aureus unless cultures
ate), but treatment without these studies is reasonable in typical yield streptococci alone (when oral penicillin is the re-
cases (strong, moderate). commended agent) (strong, high). Because S. aureus isolates
2. Bullous and nonbullous impetigo can be treated with from impetigo and ecthyma are usually methicillin suscepti-
oral or topical antimicrobials, but oral therapy is recommended ble, dicloxacillin or cephalexin is recommended. When
for patients with numerous lesions or in outbreaks affecting sev- MRSA is suspected or conrmed, doxycycline, clindamycin,
eral people to help decrease transmission of infection. Treat- or sulfamethoxazole-trimethoprim (SMX-TMP) is recom-
ment for ecthyma should be an oral antimicrobial. mended (strong, moderate).
(c) Systemic antimicrobials should be used for infections
(a) Treatment of bullous and nonbullous impetigo should during outbreaks of poststreptococcal glomerulonephritis to
be with either mupirocin or retapamulin twice daily (bid) help eliminate nephritogenic strains of S. pyogenes from the
for 5 days (strong, high). community (strong, moderate).
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e11
Figure 2. Algorithm for the management and treatment of surgical site infections (SSIs). *For patients with type 1 (anaphylaxis or hives) allergy to -lactam
antibiotics. If Gram stain not available, open and debride if purulent drainage present. Where the rate of infection with methicillin-resistant Staphylococcus
aureus infection is high, consider vancomycin, daptomycin, or linezolid, pending results of culture and susceptibility tests. Adapted and modied with permis-
sion from Dellinger et al [96]. Abbreviations: GI, gastrointestinal; MRSA, methicillin-resistant Staphylococcus aureus ; WBC, white blood cell count.
II. What Is the Appropriate Evaluation and Treatment for Purulent 4. Gram stain and culture of pus from inamed epidermoid
SSTIs (Cutaneous Abscesses, Furuncles, Carbuncles, and cysts are not recommended (strong, moderate).
Inamed Epidermoid Cysts)? 5. Incision and drainage is the recommended treatment for
Recommendations inamed epidermoid cysts, carbuncles, abscesses, and large fu-
3. Gram stain and culture of pus from carbuncles and ab- runcles, mild (Figure 1) (strong, high).
scesses are recommended, but treatment without these studies 6. The decision to administer antibiotics directed against
is reasonable in typical cases (strong, moderate). S. aureus as an adjunct to incision and drainage should be
made based upon presence or absence of systemic inamma- antibiotic active against MRSA is recommended for patients
tory response syndrome (SIRS), such as temperature >38C or with carbuncles or abscesses who have failed initial antibiotic
<36C, tachypnea >24 breaths per minute, tachycardia >90 treatment or have markedly impaired host defenses or in pa-
beats per minute, or white blood cell count >12 000 tients with SIRS and hypotension (severe; Figure 1 and
or <400 cells/L (moderate; Figure 1) (strong, low). An Table 2) (strong, low).
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e13
e14
Table 2. Antimicrobial Therapy for Staphylococcal and Streptococcal Skin and Soft Tissue Infections
in 2 divided doses po
Stevens et al
Retapamulin ointment Apply to lesions bid Apply to lesions bid For patients with limited number of lesions
Mupirocin ointment Apply to lesions bid Apply to lesions bid For patients with limited number of lesions
MSSA SSTI Nafcillin or oxacillin 1-2 g every 4 h IV 100150 mg/kg/d in 4 divided doses Parental drug of choice; inactive against MRSA
Cefazolin 1 g every 8 h IV 50 mg/kg/d in 3 divided doses For penicillin-allergic patients except those with immediate
hypersensitivity reactions. More convenient than nafcillin
with less bone marrow suppression
Clindamycin 600 mg every 8 h IV 2540 mg/kg/d in 3 divided doses IV or Bacteriostatic; potential of cross-resistance and emergence
or 2530 mg/kg/d in 3 divided doses po of resistance in erythromycin-resistant strains; inducible
300450 mg qid po resistance in MRSA
Dicloxacillin 500 mg qid po 2550 mg/kg/d in 4 divided doses po Oral agent of choice for methicillin-susceptible strains in
adults. Not used much in pediatrics
Cephalexin 500 mg qid po 2550 mg/kg/d 4 divided doses po For penicillin-allergic patients except those with immediate
hypersensitivity reactions. The availability of a suspension
and requirement for less frequent dosing
Doxycycline, 100 mg bid po Not recommended for age <8 yd Bacteriostatic; limited recent clinical experience
minocycline
Trimethoprim- 12 double- 812 mg/kg (based on trimethoprim Bactericidal; efficacy poorly documented
sulfamethoxazole strength tablets component) in either 4 divided doses IV
bid po or 2 divided doses po
MRSA SSTI Vancomycin 30 mg/kg/d in 2 40 mg/kg/d in 4 divided doses IV For penicillin allergic patients; parenteral drug of choice for
divided doses IV treatment of infections caused by MRSA
Linezolid 600 mg every 12 h 10 mg/kg every 12 h IV or po for children Bacteriostatic; limited clinical experience; no cross-
IV or 600 mg bid <12 y resistance with other antibiotic classes; expensive
po
Clindamycin 600 mg every 8 h IV 2540 mg/kg/d in 3 divided doses IV or Bacteriostatic; potential of cross-resistance and emergence
or 300450 mg 3040 mg/kg/d in 3 divided doses po of resistance in erythromycin-resistant strains; inducible
qid po resistance in MRSA. Important option for children
Daptomycin 4 mg/kg every 24 h N/A Bactericidal; possible myopathy
IV
Ceftaroline 600 mg bid IV N/A Bactericidal
Doxycycline, 100 mg bid po Not recommended for age <8 yd Bacteriostatic; limited recent clinical experience
minocycline
Trimethoprim- 12 double- 812 mg/kg/d (based on trimethoprim Bactericidal; limited published efficacy data
sulfamethoxazole strength tablets component) in either 4 divided doses IV
bid po or 2 divided doses po
III. What Is the Appropriate Treatment for Recurrent Skin
Abbreviations: bid, twice daily; IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; N/A, not applicable; po, by mouth; qid, 4 times daily; SSTI, skin
Abscesses?
Recommendations
7. A recurrent abscess at a site of previous infection should
prompt a search for local causes such as a pilonidal cyst, hidra-
denitis suppurativa, or foreign material (strong, moderate).
8. Recurrent abscesses should be drained and cultured early
Comment
Doses listed are not appropriate for neonates. Refer to the report by the Committee on Infectious Diseases, American Academy of Pediatrics [246], for neonatal doses.
10. Consider a 5-day decolonization regimen twice daily of
intranasal mupirocin, daily chlorhexidine washes, and daily de-
contamination of personal items such as towels, sheets, and
clothes for recurrent S. aureus infection (weak, low).
11. Adult patients should be evaluated for neutrophil disor-
N/A
N/A
Recommendations
12. Cultures of blood or cutaneous aspirates, biopsies, or
penicillin hypersensitivity
50 mg/kg/dose
33 mg/kg/dose
every 8 h IV
every 8 h IV
every 6 h
Cefazolin 1 g every 8 h
units every 46 h IV
Penicillin VK 250500
Penicillin 24 million
Cephalexin 500 mg
mg every 6 h po
every 6 h po
Streptococcal skin
Non-purulent SSTI
moderate).
infections
(cellulitis)
d
a
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e15
16. Elevation of the affected area and treatment of predispos- >38.5C, heart rate >110 beats/minute, or white blood cell
ing factors, such as edema or underlying cutaneous disorders, (WBC) count >12 000/L (weak, low).
are recommended (strong, moderate). 24. A brief course of systemic antimicrobial therapy is indi-
17. In lower-extremity cellulitis, clinicians should carefully cated in patients with surgical site infections following clean op-
examine the interdigital toe spaces because treating ssuring, erations on the trunk, head and neck, or extremities that also
scaling, or maceration may eradicate colonization with patho- have systemic signs of infection (strong, low).
gens and reduce the incidence of recurrent infection (strong, 25. A rst-generation cephalosporin or an antistaphylococcal
moderate). penicillin for MSSA, or vancomycin, linezolid, daptomycin, tela-
18. Outpatient therapy is recommended for patients who do vancin, or ceftaroline where risk factors for MRSA are high (nasal
not have SIRS, altered mental status, or hemodynamic instabil- colonization, prior MRSA infection, recent hospitalization, recent
ity (mild nonpurulent; Figure 1) (strong, moderate). Hospitali- antibiotics), is recommended (strong, low). See also Tables 2 and 3.
zation is recommended if there is concern for a deeper or 26. Agents active against gram-negative bacteria and anaer-
necrotizing infection, for patients with poor adherence to ther- obes, such as a cephalosporin or uoroquinolone in combina-
apy, for infection in a severely immunocompromised patient, or tion with metronidazole, are recommended for infections
if outpatient treatment is failing (moderate or severe nonpuru- following operations on the axilla, gastrointestinal tract, perine-
lent; Figure 1) (strong, moderate). um, or female genital tract (strong, low). See also Table 3.
V. Should Anti-inammatory Agents Be Used to Complement VIII. What Is the Preferred Evaluation and Treatment
Antibiotic Treatment of Cellulitis? of Necrotizing Fasciitis, Including Fournier Gangrene?
Recommendation Recommendations
19. Systemic corticosteroids (eg, prednisone 40 mg daily for 27. Prompt surgical consultation is recommended for pa-
7 days) could be considered in nondiabetic adult patients with tients with aggressive infections associated with signs of system-
cellulitis (weak, moderate). ic toxicity or suspicion of necrotizing fasciitis or gas gangrene
(severe nonpurulent; Figure 1) (strong, low).
VI. What Is the Preferred Evaluation and Management of Patients 28. Empiric antibiotic treatment should be broad (eg, vanco-
With Recurrent Cellulitis? mycin or linezolid plus piperacillin-tazobactam or a carbape-
Recommendations nem; or plus ceftriaxone and metronidazole), as the etiology
20. Identify and treat predisposing conditions such as can be polymicrobial (mixed aerobicanaerobic microbes) or
edema, obesity, eczema, venous insufciency, and toe web ab- monomicrobial (group A streptococci, community-acquired
normalities (strong, moderate). These practices should be per- MRSA) (strong, low). See also Table 4.
formed as part of routine patient care and certainly during the 29. Penicillin plus clindamycin is recommended for treat-
acute stage of cellulitis (strong, moderate). ment of documented group A streptococcal necrotizing fasciitis
21. Administration of prophylactic antibiotics, such as oral (strong, low). See Figures 1, 2, and Table 4.
penicillin or erythromycin bid for 452 weeks, or intramuscular
benzathine penicillin every 24 weeks, should be considered in
IX. What Is the Appropriate Approach to the Management of
patients who have 34 episodes of cellulitis per year despite Pyomyositis?
attempts to treat or control predisposing factors (weak, moder- Recommendations
ate). This program should be continued so long as the predis- 30. Magnetic resonance imaging (MRI) is the recommended
posing factors persist (strong, moderate). imaging modality for establishing the diagnosis of pyomyositis.
Computed tomography (CT) scan and ultrasound studies are
VII. What Is the Preferred Management of Surgical Site also useful (strong, moderate).
Infections? 31. Cultures of blood and abscess material should be ob-
Recommendations tained (strong, moderate).
22. Suture removal plus incision and drainage should be per- 32. Vancomycin is recommended for initial empirical ther-
formed for surgical site infections (strong, low). apy. An agent active against enteric gram-negative bacilli should
23. Adjunctive systemic antimicrobial therapy is not routine- be added for infection in immunocompromised patients or fol-
ly indicated, but in conjunction with incision and drainage may lowing open trauma to the muscles (strong, moderate).
be benecial for surgical site infections associated with a signi- 33. Cefazolin or antistaphylococcal penicillin (eg, nafcillin or
cant systemic response (Figure 2), such as erythema and indu- oxacillin) is recommended for treatment of pyomyositis caused
ration extending >5 cm from the wound edge, temperature by MSSA (strong, moderate). See Table 2.
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e17
XIX. What Is the Appropriate Diagnosis and Treatment of Bubonic 61. Risk-stratify patients with fever and neutropenia accord-
Plague? ing to susceptibility to infection: high-risk patients are those
Recommendation with anticipated prolonged (>7 days) and profound neutropenia
51. Bubonic plague should be diagnosed by Gram stain and (absolute neutrophil count <100 cells/L) or with a Multina-
culture of aspirated material from a suppurative lymph node tional Association for Supportive Care (MASCC) score of
(strong, moderate). Streptomycin (15 mg/kg intramuscularly <21; low-risk patients are those with anticipated brief (<7
[IM] every 12 hours) or doxycycline (100 mg bid po) is recom- days) periods of neutropenia and few comorbidities (strong,
mended for treatment of bubonic plague (strong, low). Genta- low) or with a MASCC score of 21 (strong, moderate).
micin could be substituted for streptomycin (weak, low). 62. Determine the extent of infection through a thorough
physical examination, blood cultures, chest radiograph, and ad-
XX. What Is Appropriate for Diagnosis and Treatment for ditional imaging (including chest CT) as indicated by clinical
Tularemia? signs and symptoms (strong, low).
Recommendations
52. Serologic tests are the preferred method of diagnosing tu-
laremia (weak, low). XXIII. What Is the Appropriate Antibiotic Therapy for Patients With
SSTIs During the Initial Episode of Fever and Neutropenia?
53. Streptomycin (15 mg/kg every 12 hours IM) or gentami-
Recommendations
cin (1.5 mg/kg every 8 hours IV) is recommended for treatment
63. Hospitalization and empiric antibacterial therapy with
of severe cases of tularemia (strong, low).
vancomycin plus antipseudomonal antibiotics such as cefepime,
54. Tetracycline (500 mg qid) or doxycycline (100 mg bid po) is
a carbapenem (imipenem-cilastatin or meropenem or doripe-
recommended for treatment of mild cases of tularemia (strong, low).
nem) or piperacillin-tazobactam is recommended (strong, high).
55. Notify the microbiology laboratory if tularemia is suspect-
64. Documented clinical and microbiologic SSTIs should be
ed (strong, high).
treated based on antimicrobial susceptibilities of isolated organ-
isms (strong, high).
XXI. What Is the Appropriate Approach to Assess SSTIs in 65. It is recommended that the treatment duration for most
Immunocompromised Patients? bacterial SSTIs should be 714 days (strong, moderate).
Recommendations 66. Surgical intervention is recommended for drainage of
56. In addition to infection, differential diagnosis of skin le- soft tissue abscess after marrow recovery or for a progressive
sions should include drug eruption, cutaneous inltration with polymicrobial necrotizing fasciitis or myonecrosis (strong, low).
the underlying malignancy, chemotherapy- or radiation-in- 67. Adjunct colony-stimulating factor therapy (granulocyte
duced reactions, Sweet syndrome, erythema multiforme, leuko- colony-stimulating factor [G-CSF], granulocyte macrophage
cytoclastic vasculitis, and graft-vs-host disease among colony-stimulating factor [GM-CSF]) or granulocyte transfu-
allogeneic transplant recipients (strong, high). sions are not routinely recommended (weak, moderate).
57. Differential diagnosis for infection of skin lesions should 68. Acyclovir should be administered to patients suspected
include bacterial, fungal, viral, and parasitic agents (strong, high). or conrmed to have cutaneous or disseminated varicella zoster
58. Biopsy or aspiration of the lesion to obtain material for virus (herpes simplex virus [HSV] or varicella zoster virus
histological and microbiological evaluation should always be [VZV]) infection (strong, moderate).
implemented as an early diagnostic step (strong, high).
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e19
guidelines (Table 1) [2]. The following 24 clinical questions are (XXV) What is the appropriate approach to assess SSTIs in
answered: patients with cellular immunodeciency?
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e21
Cultures of the vesicle uid, pus, erosions, or ulcers establish but S. aureus alone causes a large percentage of skin abscesses,
the cause. Unless cultures yield streptococci alone, antimicrobial with a substantial number due to MRSA strains [1618].
therapy should be active against both S. aureus and streptococci Epidermoid (or epidermal inclusion) cysts, often erroneously
[12]. Oral penicillinaseresistant penicillin or rst-generation labeled sebaceous cysts, ordinarily contain skin ora in a cheesy
cephalosporins are usually effective as most staphylococcal iso- keratinous material. When inammation and purulence occur,
lates from impetigo and ecthyma are methicillin susceptible they are a reaction to rupture of the cyst wall and extrusion of its
[13]. Alternatives for penicillin-allergic patients or infections contents into the dermis, rather than an actual infectious pro-
with MRSA include doxycycline, clindamycin, or SMX-TMP. cess [19].
When streptococci alone are the cause, penicillin is the drug Incision, evacuation of pus and debris, and probing of the
of choice, with a macrolide or clindamycin as an alternative cavity to break up loculations provides effective treatment of cu-
for penicillin-allergic patients. Topical treatment with mupiro- taneous abscesses and inamed epidermoid cysts. A random-
cin [12] or retapamulin [14] is as effective as oral antimicrobials ized trial comparing incision and drainage of cutaneous
for impetigo. Clinical experience suggests that systemic therapy abscesses to ultrasonographically guided needle aspiration of
is preferred for patients with numerous lesions or in outbreaks the abscesses showed that aspiration was successful in only
affecting several people, to help decrease transmission of infec- 25% of cases overall and <10% with MRSA infections [20]. Ac-
tion [15] (Table 2). cordingly, this form of treatment is not recommended. Simply
covering the surgical site with a dry dressing is usually the eas-
iest and most effective treatment of the wound [21, 22]. Some
RECOMMENDATIONS FOR PURULENT SKIN clinicians close the wound with sutures or pack it with gauze
AND SOFT TISSUE INFECTIONS or other absorbent material. One small study, however, found
that packing caused more pain and did not improve healing
II. What Is the Appropriate Evaluation and Treatment for Purulent when compared to just covering the incision site with sterile
SSTIs (Cutaneous Abscesses, Furuncles, Carbuncles, and gauze [23].
Inamed Epidermoid Cysts)? (Figure 1)
The addition of systemic antibiotics to incision and drainage
Recommendations
of cutaneous abscesses does not improve cure rates [17, 21, 22,
3. Gram stain and culture of pus from carbuncles and ab-
24, 25], even in those due to MRSA, but did have a modest effect
scesses are recommended, but treatment without these studies
on the time to recurrence of other abscesses [17, 25]. However,
is reasonable in typical cases (strong, moderate).
systemic antibiotics should be given to patients with severely
4. Gram stain and culture of pus from inamed epidermoid
impaired host defenses or signs or symptoms of systemic infec-
cysts are not recommended (strong, moderate).
tion (Figure 1, Table 2). In addition, multiple abscesses, ex-
5. Incision and drainage is the recommended treatment for
tremes of age, and lack of response to incision and drainage
inamed epidermoid cysts, carbuncles, abscesses, and large fu-
alone are additional settings in which systemic antimicrobial
runcles (strong, high).
therapy should be considered.
6. The decision to administer antibiotics directed against
Furuncles and Carbuncles. Furuncles (or boils) are in-
S. aureus as an adjunct to incision and drainage should
fections of the hair follicle, usually caused by S. aureus, in
be made based on the presence or absence of systemic inam-
which suppuration extends through the dermis into the subcu-
matory response syndrome (SIRS) such as temperature >38C
taneous tissue, where a small abscess forms. They differ from
or <36C, tachypnea >24 breaths per minute, tachycardia >90
folliculitis, in which the inammation is more supercial and
beats per minute, or white blood cell count >12 000 or <400
pus is limited to the epidermis. Clinically, furuncles are in-
cells/L (moderate; Figure 1) (strong, low). An antibiotic
ammatory nodules with overlying pustules through which
active against MRSA is recommended for patients with car-
hair emerges. Infection involving several adjacent follicles pro-
buncles or abscesses who have markedly impaired host
duces a carbuncle, a coalescent inammatory mass with pus
defenses and in patients with SIRS (Figure 1, Table 2)
draining from multiple follicular orices. Carbuncles develop
(strong, low).
most commonly on the back of the neck, especially in individ-
Evidence Summary uals with diabetes. These are typically larger and deeper than
Cutaneous Abscesses. Cutaneous abscesses are collections of furuncles.
pus within the dermis and deeper skin tissues. They are usually Furuncles often rupture and drain spontaneously or follow-
painful, tender, and uctuant red nodules, often surmounted by ing treatment with moist heat. Most large furuncles and all car-
a pustule and encircled by a rim of erythematous swelling. Cu- buncles should be treated with incision and drainage. Systemic
taneous abscesses can be polymicrobial, containing regional antimicrobials are usually unnecessary, unless fever or other ev-
skin ora or organisms from the adjacent mucous membranes, idence of systemic infection is present (Figure 1).
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e23
if outpatient treatment is failing (moderate or severe nonpuru- abscesses, and the determination of whether isolates are patho-
lent; Figure 1) (strong, moderate). gens or contaminants.
Cultures of punch biopsy specimens yield an organism in
Evidence Summary 20%30% of cases [39, 47], but the concentration of bacteria
Cellulitis and erysipelas refer to diffuse, supercial, spread- in the tissues is usually quite low [47]. Combined data from
ing skin infections. The term cellulitis is not appropriate for specimen cultures, serologic studies [41, 4851], and other
cutaneous inammation associated with collections of pus, such methods (eg, immunohistochemical staining to detect antigens
as in septic bursitis, furuncles, or skin abscesses. For example, in skin biopsies [51, 52]), suggests that the vast majority of these
when cutaneous redness, warmth, tenderness, and edema en- infections arise from streptococci, often group A, but also from
circle a suppurative focus such as an infected bursa, the appro- other groups, such as B, C, F, or G. The source of these patho-
priate terminology is septic bursitis with surrounding gens is frequently unclear, but in many cases of leg cellulitis, the
inammation, rather than septic bursitis with surrounding responsible streptococci reside in macerated, scaly, or ssured
cellulitis. This distinction is clinically crucial, for the primary interdigital toe spaces [53, 54]. This observation underscores
treatment of cellulitis is antimicrobial therapy, whereas for pu- the importance of detecting and treating tinea pedis, erythras-
rulent collections the major component of management is ma, and other causes of toe web abnormalities. Occasionally,
drainage of the pus, with antimicrobial therapy either being un- the reservoir of streptococci is the anal canal [55] or the vagina,
necessary or having a subsidiary role (Figure 1 and Table 2). especially for group B streptococcal cellulitis in patients with
The term erysipelas has 3 different meanings: (1) for some, previous gynecologic cancer treated with surgery and radiation
erysipelas is an infection limited to the upper dermis, including therapy. Staphylococcus aureus less frequently causes cellulitis,
the supercial lymphatics, whereas cellulitis involves the deeper but cases due to this organism are typically associated with an
dermis and subcutaneous fat, and on examination erysipelas open wound or previous penetrating trauma, including sites of
putatively has more clearly delineated borders of inammation illicit drug injection. Several other organisms can cause celluli-
than cellulitis; (2) for many, erysipelas has been used to refer to tis, but usually only in special circumstances, such as animal
cellulitis involving the face only; and (3) for others, especially in bites, freshwater or saltwater immersion injuries, neutropenia,
European countries, cellulitis and erysipelas are synonyms [35]. or severe cell-mediated immunodeciency.
These infections cause rapidly spreading areas of erythema, Cultures of blood, tissue aspirates, or skin biopsies are unnec-
swelling, tenderness, and warmth, sometimes accompanied by essary for typical cases of cellulitis. Blood cultures should be ob-
lymphangitis and inammation of the regional lymph nodes. tained and cultures of skin biopsy or aspirate considered for
The skin surface may resemble an orange peel ( peau dorange) patients with malignancy, severe systemic features (such as
due to supercial cutaneous edema surrounding hair follicles high fever and hypotension), and unusual predisposing factors,
and causing skin dimpling because the follicles remain tethered such as immersion injury, animal bites, neutropenia, and severe
to the underlying dermis. Vesicles, bullae, and cutaneous hem- cell-mediated immunodeciency [42].
orrhage in the form of petechiae or ecchymoses may develop. Therapy for typical cases of cellulitis should include an antibi-
Systemic manifestations are usually mild, but fever, tachycardia, otic active against streptococci (Table 2). A large percentage of
confusion, hypotension, and leukocytosis are sometimes pre- patients can receive oral medications from the start for typical
sent and may occur hours before the skin abnormalities appear. cellulitis [56], and suitable antibiotics for most patients include
These infections arise when microbes breach the cutaneous penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin,
surface, especially in patients with fragile skin or diminished cephalexin, or clindamycin. In cases of uncomplicated cellulitis,
local host defenses from such conditions as obesity, previous a 5-day course of antimicrobial therapy is as effective as a 10-day
cutaneous trauma (including surgery), prior episodes of cellu- course, if clinical improvement has occurred by 5 days [57]. In a
litis, and edema from venous insufciency or lymphedema retrospective study of cellulitis and abscesses requiring hospital-
[36, 37]. The origin of the disrupted skin surface may be obvi- ization, the average duration of treatment was 2 weeks and only
ous, such as trauma, ulceration, and preexisting cutaneous in- about one-third of patients received specic treatment for gram-
ammation, but often the breaks in the skin are small and positive pathogens [58]. Two-thirds received very-broad-spec-
clinically unapparent. These infections are most common on trum treatment, and the failure rate of 12% was not different re-
the lower legs. Blood cultures are generally positive in 5% of gardless of spectrum of treatment. In some patients, cutaneous
cases [38]. The yield of cultures of needle aspirations of the in- inammation and systemic features worsen after initiating ther-
amed skin ranges from 5% to approximately 40% [3946]. apy, probably because sudden destruction of the pathogens re-
The differences in diagnostic sensitivity and specicity are leases potent enzymes that increase local inammation.
due to the variety of patient populations studied, the denitions MRSA is an unusual cause of typical cellulitis. A prospective
of cellulitis, the inclusion or exclusion of cases with associated study of patients with cellulitis in a medical center with a high
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e25
twice daily for 12 months increased the time to recurrence to of the surgery, and are documented with at least 1 of the follow-
626 days compared with 532 days in the control group and de- ing: (1) purulent incisional drainage, (2) positive culture of
creased the frequency of recurrence from 37% to 22% [76]. aseptically obtained uid or tissue from the supercial
wound, (3) local signs and symptoms of pain or tenderness,
swelling, and erythema after the incision is opened by the sur-
RECOMMENDATIONS FOR SURGICAL SITE
geon (unless culture negative), or (4) diagnosis of SSI by the at-
INFECTIONS
tending surgeon or physician based on their experience and
expert opinion. A deep incisional infection involves the deeper
VII. What Is the Preferred Management of Surgical Site
Infections?
soft tissue (eg, fascia and muscle), and occurs within 30 days of
Recommendations the operation or within 1 year if a prosthesis was inserted and
22. Suture removal plus incision and drainage should be per- has the same ndings as described for a supercial incisional
formed for surgical site infections (strong, low). SSI. An organ/space SSI has the same time constraints and ev-
23. Adjunctive systemic antimicrobial therapy is not routine- idence for infection as a deep incisional SSI, and it may involve
ly indicated, but in conjunction with incision and drainage may any part of the anatomy (organs or spaces) other than the orig-
be benecial for surgical site infections associated with a signi- inal surgical incision [78]. Examples would include postopera-
cant systemic response (Figure 2) such as erythema and indura- tive peritonitis, empyema, or joint space infection. Any deep SSI
tion extending >5 cm from the wound edge, temperature >38.5 that does not resolve in the expected manner following treat-
C, heart rate >110 beats/minute, or white blood cell (WBC) ment should be investigated as a possible supercial manifesta-
count >12 000/L (weak, low). tion of a deeper organ/space infection. Diagnosis and treatment
24. A brief course of systemic antimicrobial therapy is indi- of organ space infections in the abdomen are discussed in other
cated in patients with surgical site infections following clean op- guidelines. Tedizolid and dalbavancin are also effective treat-
erations on the trunk, head and neck, or extremities that also ments of SSTI including those caused by MRSA and may be ap-
have systemic signs of infection (strong, low). proved by the US Food and Drug Administration (FDA) in June
25. A rst-generation cephalosporin or an antistaphylococ- 2014.
cal penicillin for methicillin-susceptible Staphylococcus aureus Local signs of pain, swelling, erythema, and purulent drain-
(MSSA) or vancomycin, linezolid, daptomycin, telavancin, or age provide the most reliable information in diagnosing an SSI.
ceftaroline where risk factors for MRSA are high (nasal coloni- In morbidly obese patients or in those with deep, multilayer
zation, prior MRSA infection, recent hospitalization, recent an- wounds such as after thoracotomy, external signs of SSI may
tibiotics) is recommended (strong, low). be delayed. While many patients with a SSI will develop fever,
26. Agents active against gram-negative bacteria and anaer- it usually does not occur immediately postoperatively, and in
obes, such as a cephalosporin or uoroquinolone in combina- fact, most postoperative fevers are not associated with an SSI
tion with metronidazole are recommended for infections [80]. Flat, erythematous skin changes can occur around or
following operations on the axilla, gastrointestinal (GI) tract, near a surgical incision during the rst week without swelling
perineum, or female genital tract (Table 2) (strong, low). or wound drainage. Most resolve without any treatment. The
cause is unknown but may relate to tape sensitivity or other
Evidence Summary local tissue insult not involving bacteria. Numerous experimen-
Wound infections, or surgical site infections (SSIs) are the most tal studies and clinical trials demonstrate that antibiotics begun
common adverse event affecting hospitalized surgical patients immediately postoperatively or continued for long periods after
[77]. Data from the National Nosocomial Infection Surveillance the procedure do not prevent or cure this inammation or in-
System (NNIS) show an average incidence of SSI of 2.6%, ac- fection [8188]. Therefore, the suspicion of possible SSI does
counting for 38% of nosocomial infections in surgical patients not justify use of antibiotics without a denitive diagnosis
[78]. The frequency of SSI is clearly related to the category of and the institution of other therapeutic measures such as open-
operation, with clean and low-risk operations (by NNIS classi- ing the wound (Figure 2).
cation) having the lowest incidence, and contaminated and SSIs rarely occur during the rst 48 hours after surgery, and
high-risk operations having higher infection rates [79]. Unfor- fever during that period usually arises from noninfectious or
tunately, there are no studies that have objectively compared unknown causes. SSIs that do occur in this time frame are al-
treatments for SSI. most always due to S. pyogenes or Clostridium species. After
SSIs are divided into the categories of supercial incisional 48 hours, SSI is a more common source of fever, and careful in-
SSI, deep incisional SSI, and organ/space SSI [78]. Supercial spection of the wound is indicated; by 4 days after surgery, a
incisional SSIs involve only the subcutaneous space, between fever is equally likely to be caused by an SSI or by another in-
the skin and underlying muscular fascia, occur within 30 days fection or other unknown sources [80]. Later infections are less
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e27
Table 3. Antibiotics for Treatment of Incisional Surgical Site muscular fascia or aponeurosis is involved, but in fact it is the
Infections supercial fascia that is most commonly involved.
ceftriaxone 1 to 2 g every 24 h IV
CID 2014:59 (15 July)
Vibrio vulnificus Doxycycline 100 mg every 12 h Not recommended for children but may need N/A
plus IV to use in life-threatening situations
ceftriaxone 1 g qid IV
or 2 g tid IV
cefotaxime
Abbreviations: IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus; N/A, not applicable; qid, 4 times daily; tid, 3 times daily.
a
If staphylococcus present or suspected, add an appropriate agent.
b
If MRSA is present or suspected, add vancomycin not to exceed the maximum adult daily dose.
e29
numerous different anaerobic and aerobic organisms can be cul- patient. Biopsy for frozen section analysis may also be used to
tured from the involved fascial plane, with an average of 5 path- make the diagnosis, but, if enough suspicion exists to do a biopsy,
ogens in each wound. Most of the organisms originate from the the diagnosis is usually evident on gross inspection without his-
bowel or genitourinary ora (eg, coliforms and anaerobic tologic conrmation. In addition, sampling errors of biopsy
bacteria). alone may produce a false-negative result.
Diagnosis Treatment
The diagnosis of fasciitis may not be apparent upon rst seeing Surgical intervention is the primary therapeutic modality in
the patient. Overlying cutaneous inammation may resemble cases of necrotizing fasciitis and is indicated when this infection
cellulitis. However, features that suggest involvement of deeper is conrmed or suspected. Features suggestive of necrotizing
tissues include (1) severe pain that seems disproportional to the fasciitis include (1) the clinical ndings described above; (2)
clinical ndings; (2) failure to respond to initial antibiotic ther- failure of apparently uncomplicated cellulitis to respond to an-
apy; (3) the hard, wooden feel of the subcutaneous tissue, ex- tibiotics after a reasonable trial; (3) profound toxicity; fever, hy-
tending beyond the area of apparent skin involvement; (4) potension, or advancement of the SSTI during antibiotic
systemic toxicity, often with altered mental status; (5) edema therapy; (4) skin necrosis with easy dissection along the fascia
or tenderness extending beyond the cutaneous erythema; (6) by a blunt instrument; or (5) presence of gas in the soft tissues.
crepitus, indicating gas in the tissues; (7) bullous lesions; and Most patients with necrotizing fasciitis should return to the
(8) skin necrosis or ecchymoses. operating room 2436 hours after the rst debridement and
Computed tomography (CT) or magnetic resonance imaging daily thereafter until the surgical team nds no further need
(MRI) may show edema extending along the fascial plane, al- for debridement. Although discrete pus is usually absent,
though the sensitivity and specicity of these imaging studies these wounds can discharge copious amounts of tissue uid,
are ill dened. CT or MRI also may delay denitive diagnosis and aggressive uid administration is a necessary adjunct.
and treatment. In practice, clinical judgment is the most impor- In the absence of denitive clinical trials, antimicrobial ther-
tant element in diagnosis. The most important diagnostic feature apy should be administered until further debridement is no lon-
of necrotizing fasciitis is the appearance of the subcutaneous tis- ger necessary, the patient has improved clinically, and fever has
sues or fascial planes at operation. The fascia at the time of direct been absent for 4872 hours. Empiric treatment of polymicro-
visual examination is swollen and dull gray in appearance with bial necrotizing fasciitis should include agents effective against
stringy areas of necrosis; a thin, brownish exudate may be pre- both aerobes, including MRSA, and anaerobes (Table 4).
sent. Even after deep dissection, there is typically no true pus de- Among the many choices is vancomycin, linezolid, or daptomycin
tected. Extensive undermining of surrounding tissues is usually combined with one of the following options: (1) piperacillin-
present, and the tissue planes can be readily dissected with a tazobactam, (2) a carbapenem (imipenem-cilastatin, meropenem,
gloved nger or a blunt instrument. Several clinical scoring sys- and ertapenem), (3) ceftriaxone plus metronidazole, or (4) a u-
tems have been proposed, but all of these are more useful for ex- oroquinolone plus metronidazole (Table 4). Once the microbial
cluding necrotizing soft tissue infections than identifying them. etiology has been determined, the antibiotic coverage should be
A high index of suspicion remains paramount [111]. appropriately modied.
A denitive bacteriologic diagnosis is best established by cul- Necrotizing fasciitis and/or streptococcal toxic shock syn-
ture and Gram stain of deep tissue obtained at operation or by drome caused by group A streptococci should be treated with
positive blood cultures. Cultures of the supercial wound may both clindamycin and penicillin. Clindamycin suppresses strep-
be misleading because results may not reect organisms in the tococcal toxin and cytokine production. Clindamycin was
deep tissue infection. Direct needle aspiration of an area of cu- found to be superior to penicillin in animal models, and 2 ob-
taneous inammation may yield uid for Gram stain and cul- servational studies show greater efcacy for clindamycin than -
ture. In suspected cases a small, exploratory incision made in lactam antibiotics [112, 113]. Penicillin should be added because
the area of maximum suspicion can be useful for excluding or of potential resistance of group A streptococci to clindamycin.
conrming the diagnosis. Gram stains of the exudate will Macrolide resistance in the United States is <5.0% among group
demonstrate the pathogens and provide an early guide to anti- A streptococci [114], but in Germany macrolide resistance is
microbial therapy. Gram-positive cocci in chains suggest Strep- 8.2%, and in Spain 18.3% [115, 116]. Some of these strains are
tococcus (either group A or anaerobic). Large gram-positive also clindamycin resistant. Interestingly, in the United States, no
cocci in clusters suggest S. aureus. If a necrotizing infection is resistance to clindamycin was found from invasive strains of
present, it will be obvious from the ndings described above. group A streptococci in Chicago [117].
If there is no necrosis on exploratory incision, the procedure The efcacy of intravenous immunoglobulin (IVIG) in
can be terminated with very little risk or morbidity to the treating streptococcal toxic shock syndrome has not been
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e31
normal in patients with a single area of pyomyositis related to histolyticum, or Clostridium septicum. Clostridium perfringens
hematogenous seeding of muscle [124]. is the most frequent cause of trauma-associated gas gangrene
MRI is the imaging modality that demonstrates pyomyositis [136]. Increasingly severe pain beginning within 24 hours at
most effectively [128, 129]. Muscle inammation and abscess for- the injury site is the rst reliable clinical symptom. The skin
mation are readily noted; other sites of infection such as osteomy- may initially appear pale, but quickly changes to bronze, then
elitis or septic arthritis may also be observed or a venous purplish-red. The infected region becomes tense and tender,
thrombosis detected [130, 131]. In patients with disseminated S. and bullae lled with reddish-blue uid appear. Gas in the tis-
aureus infection, multiple small areas of pyomyositis may become sue, detected as crepitus or by imaging, is usually present by this
apparent. If an MRI cannot be performed, a CT scan can be use- late stage. Signs of systemic toxicity, including tachycardia,
ful, but it lacks the detail seen with MRI. Ultrasound is helpful if fever, and diaphoresis, develop rapidly, followed by shock and
the infected muscle groups are supercial. Plain radiographs are multiple organ failure.
sometimes used, but may demonstrate only soft tissue swelling. Spontaneous gangrene, in contrast to trauma-associated gan-
In most cases of abscess, drainage is critical for optimal ther- grene, is principally associated with the more aerotolerant C.
apy [132]. Given the prevalence of community-acquired MRSA septicum and occurs predominantly in patients with neutrope-
in the United States [124, 132], vancomycin is recommended nia or gastrointestinal malignancy. It develops in normal soft
for initial empirical therapy. Other agents active against MRSA tissue in the absence of trauma as a result of hematogenous
(eg, linezolid, daptomycin, telavancin, or ceftaroline; clindamycin spread from a colonic lesion, usually cancer. A rather innocuous
for susceptible isolates) may also be effective; however, clinical early lesion evolves over the course of 24 hours into an infection
data are lacking because pyomyositis was an exclusion in ran- with all of the cardinal manifestations of gas gangrene. The di-
domized trials comparing these agents to vancomycin in treating agnosis is frequently not considered until gas is detected in
complicated SSTIs [133135]. Cefazolin or antistaphylococcal tissue or systemic signs of toxicity appear. Early surgical inspec-
penicillin is recommended for denitive therapy of pyomyositis tion and debridement are necessary, and tissue Gram stain
caused by MSSA. A broader spectrum of organisms causes shows large, gram-positive or gram-variable rods at the site of
pyomyositis in patients with underlying conditions [126], and infection [136].
empirical coverage with vancomycin plus 1 of the following Clostridial gas gangrene is a fulminant infection that requires
is recommended: (a) piperacillin-tazobactam, (b) ampicillin- meticulous intensive care, supportive measures, emergent surgi-
sulbactam, or (c) a carbapenem antimicrobial. cal debridement, and appropriate antibiotics. Because bacteria
other than clostridia produce tissue gas, initial coverage should
be broad as for necrotizing fasciitis until the diagnosis is estab-
RECOMMENDATIONS FOR EVALUATION AND
lished by culture or Gram stain. Treatment of experimental gas
TREATMENT OF CLOSTRIDIAL GAS GANGRENE
gangrene has demonstrated that tetracycline, clindamycin, and
AND MYONECROSIS
chloramphenicol are more effective than penicillin [137, 138].
Because 5% of strains of C. perfringens are clindamycin resis-
X. What Is the Appropriate Approach to the Evaluation and
Treatment of Clostridial Gas Gangrene or Myonecrosis?
tant, the combination of penicillin plus clindamycin is the rec-
Recommendations ommended antibiotic treatment [137, 138].
37. Urgent surgical exploration of the suspected gas gangrene The value of adjunctive HBO treatment for gas gangrene is
site and surgical debridement of involved tissue should be per- controversial [139]. HBO is advocated on the basis of laboratory
formed (severe nonpurulent; Figure 1) (strong, moderate). studies showing that it suppressed log-phase growth of C. per-
38. In the absence of a denitive etiologic diagnosis, broad- fringens, but not the more aerotolerant C. septicum [140, 141].
spectrum treatment with vancomycin plus either piperacillin- Studies in animal models demonstrate little efcacy of HBO
tazobactam, ampicillin-sulbactam, or a carbapenem antimicro- when used alone, whereas antibiotics alone, especially those
bial is recommended (strong, low). Denitive antimicrobial that inhibit bacterial protein synthesis, have marked benet
therapy along with penicillin and clindamycin is recommended [139].
for treatment of clostridial myonecrosis (strong, low). Clinical data for a role of HBO are very poor quality and are
39. Hyperbaric oxygen (HBO) therapy is not recommended entirely based on uncontrolled, observational case series [142].
because it has not been proven as a benet to the patient and The absence of criteria to identify patients who may benet
may delay resuscitation and surgical debridement (strong, low). from HBO therapy, the appropriate time to initiate therapy,
and its association with serious adverse events are additional
Evidence Summary concerns [142, 143].
Clostridial gas gangrene or myonecrosis is most commonly caused Emergent and aggressive surgical debridement and adminis-
by Clostridium perfringens, Clostridium novyi, Clostridium tration of systemic antimicrobials are the cornerstones of
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e33
Table 5. Recommended Therapy for Infections Following Animal or Human Bites
Therapy Type
Antimicrobial Agent by
Type of Bite Oral Intravenous Comments
Animal bite
Amoxicillin-clavulanate 875/125 mg bid ... Some gram-negative rods are resistant; misses MRSA
Ampicillin-sulbactam ... 1.53.0 g every 68 h Some gram-negative rods are resistant; misses MRSA
Piperacillin-tazobactam ... 3.37 g every 68 h Misses MRSA
Carbapenems See individual info. Misses MRSA
Doxycycline 100 mg bid 100 mg every 12 h Excellent activity against Pasteurella multocida; some
streptococci are resistant
Penicillin plus 500 mg qid/500 mg qid ...
dicloxacillin
SMX-TMP 160800 mg bid 510 mg/kg/day of TMP Good activity against aerobes; poor activity against
component anaerobes
Metronidazole 250500 mg tid 500 mg every 8 h Good activity against anaerobes; no activity against aerobes
Clindamycin 300 mg tid 600 mg every 68 h Good activity against staphylococci, streptococci, and
anaerobes; misses P. multocida
Second-generation Good activity against P. multocida; misses anaerobes
cephalosporin
Cefuroxime 500 mg bid 1 g every 12 h
Cefoxitin ... 1 g every 68 h
Third-generation cephalosporin
Ceftriaxone ... 1 g every 12 h
Cefotaxime ... 12 g every 68 h
Fluoroquinolones Good activity against P. multocida; misses MRSA and some
anaerobes
Ciprooxacin 500750 mg bid 400 mg every 12 h
Levofloxacin 750 mg daily 750 mg daily
Moxioxacin 400 mg daily 400 mg daily Monotherapy; good for anaerobes also
Human bite
Amoxicillin-clavulanate 875/125 mg bid ... Some gram-negative rods are resistant; misses MRSA
Ampicillin-sulbactam ... 1.53.0 g every 6 h Some gram-negative rods are resistant; misses MRSA
Carbapenems Misses MRSA
Doxycycline 100 mg bid ... Good activity against Eikenella species, staphylococci, and
anaerobes; some streptococci are resistant
Abbreviations: bid, twice daily; MRSA, methicillin-resistant Staphylococcus aureus; qid, 4 times daily; SMX-TMP, sulfamethoxazole-trimethoprim; tid, 3 times daily.
streptococci, S. aureus, and Eikenella corrodens, as well as with isolates per wound and whether additional coverage for anaer-
multiple anaerobic organisms, including Fusobacterium, Pep- obes is required.
tostreptococcus, Prevotella, and Porphyromonas species. Eikenel-
la corrodens is resistant to rst-generation cephalosporins,
XIII. Should Tetanus Toxoid Be Administered for Animal Bite
macrolides, clindamycin, and aminoglycosides (Table 5). Wounds?
Therefore, treatment with amoxicillin-clavulanate, ampicillin- Recommendation
sulbactam, or ertapenem is recommended; if there is history 43. Tetanus toxoid should be administered to patients with-
of hypersensitivity to -lactams, a uoroquinolone, such as cip- out toxoid vaccination within 10 years. Tetanus, diptheria, and
rooxacin or levooxacin plus metronidazole, or moxioxacin pertussis (Tdap) is preferred over Tetanus and diptheria (Td) if
as a single agent is recommended. Broader empirical coverage the former has not been previously given (strong, low).
for abscesses might yield better therapeutic results. Additional-
ly, a more focused therapy for nonpurulent infected wounds Evidence Summary
could allow narrower therapy. Cultures are often not done on Tetanus is a severe and often fatal disease preventable through
wounds, and empirical therapy might miss pathogens. The bac- routine vaccination (ie, primary series and decennial boosters).
teriology of these wounds can differentiate the number of The incidence of tetanus in the United States has declined
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e35
Airway compromise requiring intubation or tracheostomy may azithromycin for patients weighing 45.5 kg (100 lb) is 500 mg
occur with malignant edema. on day 1, then 250 mg once daily for 4 additional days; for
those weighing <45.5 kg, the dose is 10 mg/kg orally on day 1,
RECOMMENDATIONS FOR EVALUATION AND then 5 mg/kg on days 25 [124]. Cutaneous bacillary angiomato-
TREATMENT OF BACILLARY ANGIOMATOSIS sis therapy has not been systematically examined. Based on case
AND CAT SCRATCH DISEASE reports and small series, either erythromycin (500 mg qid) or
doxycycline (100 mg bid) appears effective [171]. The duration
XVI. What Is the Appropriate Approach for the Evaluation and of initial therapy, while not standardized, should be for 2 weeks
Treatment of Bacillary Angiomatosis and Cat Scratch Disease? to 2 months. With relapses, retreatment with prolonged therapy
Recommendations (months) should be entertained until immunocompetence re-
47. Azithromycin is recommended for cat scratch disease turns. HIV-infected patients may require lifelong treatment [171].
(strong, moderate) according to the following dosing protocol:
XVII. What Is the Preferred Treatment for Erysipeloid?
(a) Patients >45 kg: 500 mg on day 1 followed by 250 mg
Recommendation
for 4 additional days (strong, moderate).
49. Penicillin (500 mg qid) or amoxicillin (500 mg 3 times
(b) Patients <45 kg: 10 mg/kg on day 1 and 5 mg/kg for 4
daily [tid]) for 710 days is recommended for treatment of er-
more days (strong, moderate).
ysipeloid (strong, high).
48. Erythromycin 500 mg qid or doxycycline 100 mg bid for
2 weeks to 2 months is recommended for treatment of bacillary Evidence Summary
angiomatosis (strong, moderate). Erysipeloid is a cutaneous infection caused by Erysipelothrix
rhusiopathiae a thin, pleomorphic, non-spore-forming gram-
Evidence Summary
positive rod. It is a zoonosis acquired by handling sh, marine
In classic cat scratch disease, a papule or pustule develops from
animals, swine, or poultry. One day to 7 days after exposure, a
330 days following a scratch or a bite. Lymph nodes that drain
red maculopapular lesion develops, usually on ngers or hands.
the infected area enlarge about 3 weeks after inoculation. The
Erythema spreads centrifugally, with central clearing. A blue
disease course varies, but lymphadenopathy generally resolves
ring with a peripheral red halo may appear, giving the lesion
within 16 months. In about 10% of cases, the nodes suppurate.
a target appearance. Regional lymphangitis/lymphadenopathy
Extranodal disease (eg, central nervous system, liver, spleen,
occurs in about one-third of cases. A severe generalized cutane-
bone, and lung) develops in 2% of cases. Bartonella henselae
ous variety also occurs. Systemic symptoms and leukocytosis are
causes most cases of cat scratch disease in immunocompetent
unusual. Culture of an aspirate and/or biopsy of the lesion es-
hosts. Bacillary angiomatosis, seen in immunocompromised pa-
tablish the diagnosis; blood cultures are rarely positive. Untreat-
tients, especially with AIDS, can occur from either B. henselae
ed erysipeloid resolves over about 34 weeks, but treatment
or Bartonella quintana.
probably hastens healing and may reduce systemic complica-
Bacillary angiomatosis typically occurs in individuals with
tions. Based on in vitro susceptibilities and anecdotal experienc-
AIDS and has 2 clinical appearances: (1) red papules that
es, penicillin is appropriate. Cephalosporins, clindamycin, or
vary in size from a millimeter to several centimeters, numbering
uoroquinolones should be effective for those intolerant of pen-
from 1 to >1000; (2) subcutaneous, painful nodules with the
icillin. Erysipelothrix rhusiopathiae is resistant to vancomycin,
overlying skin having a normal or dusky hue.
teicoplanin, and daptomycin [133, 134, 172, 173].
Diagnosis of Bartonella infections may be difcult because
the organism is fastidious and difcult to grow in culture. Sero- XVIII. What Is the Appropriate Treatment of Glanders?
logical testing supports the diagnosis, although there is cross- Recommendation
reactivity between B. henselae and B. quintana as well as with 50. Ceftazidime, gentamicin, imipenem, doxycycline, or cip-
a few other organisms. PCR is a diagnostic option. A positive rooxacin is recommended based on in vitro susceptibility
Warthin-Starry silver stain of infected lymph node tissue is use- (strong, low).
ful to conrm the diagnosis, although it cannot differentiate
species of Bartonella. Evidence Summary
Treatment of cat scratch disease with antimicrobial agents Glanders, characterized by ulcerating nodular lesions of the skin
has had variable, but rarely dramatic, results. A single, dou- and mucous membrane, is caused by the aerobic gram-negative
ble-blind placebo-controlled study involved 29 patients, 14 of rod Burkholderia mallei. Glanders is mainly a disease mainly
whom received azithromycin [170]. The lymph node size re- of solipeds (eg, horses and mules). Humans become acci-
gressed by 80% at 30 days more frequently in the azithromy- dental hosts either by inhalation or skin contact. Although
cin-treated patients (P = .02). The recommended dose of other organs may be involved, pustular skin lesions and
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e37
function. For children, streptomycin should be administered at pathogenic in normal hosts (opportunistic organisms such as
30 mg/kg/day in 2 divided doses or gentamicin at 6 mg/kg/day Aspergillus fumigatus). However, infectious agents commonly
in 3 divided doses [130]. Although no data exist, treatment with found in immunocompetent patients (eg, S. pyogenes,
a parenteral agent until the acute illness is controlled, followed S. aureus) still need to be entertained in the differential diagno-
by an oral agent, seems rational for the duration of 710 days. sis of skin and soft tissue lesions in immunocompromised pa-
Treatment of severe cases should be extended to 14 days. tients even if the dermatological ndings are atypical for these
For mild to moderate disease, oral tetracycline (500 mg qid) common organisms. A careful epidemiologic history (eg, expo-
or doxycycline (100 mg bid) is appropriate. A few cases have sure to raw seafood, pets, and travel) should also be obtained in
been treated with uoroquinolones with mixed results [177]. these patients to consider organisms potentially associated with
Oral levooxacin (500 mg daily) or ciprooxacin (750 mg these exposures when appropriate (eg, V. vulnicus, B. henselae,
bid) in adults may be reasonable in mild to moderate illness. cutaneous leishmaniasis). Use of antimicrobial prophylaxis in
For oral regimens, patients should receive at least 14 days of these patients has shown to ultimately impact the pathogens
therapy. Despite clinical responses and appropriate treatment that will be isolated when infection develops, and this informa-
in one study from France, 38.6% of patients relapsed [177]. tion should be available to the clinician when assessing im-
munocompromised patients with skin and soft tissue lesions
[182, 183].
XXI. What Is the Appropriate Approach to Assess SSTIs in
Immunocompromised Patients?
After considering the important specic factors concerning
Recommendations the patients immunocompromised status (eg, neutropenia or
56. In addition to infection, differential diagnosis of skin le- neutrophil defects, cellular immune defect, presence of intravas-
sions should include drug eruption, cutaneous inltration with cular catheters) [180, 181], the gross morphologic characteristics
the underlying malignancy, chemotherapy- or radiation-in- of the skin lesion(s) should be characterized, the extent of the
duced reactions, Sweet syndrome, erythema multiforme, leuko- infection determined (eg, localized vs disseminated), and ap-
cytoclastic vasculitis, and graft-vs-host disease among propriate diagnostic tests undertaken to identify the infecting
allogeneic transplant recipients (strong, high). pathogen. Although blood cultures, tests for detection of anti-
57. Differential diagnosis for infection of skin lesions should gens in blood or vesicular uid, or nucleic acid amplication
include bacterial, fungal, viral, and parasitic agents (strong, techniques in body uids or tissues may be helpful, the most
high). specic method for an expedited diagnosis is biopsy or aspira-
58. Biopsy or aspiration of the lesion to obtain material for tion of the lesion to obtain material for histological and micro-
histological and microbiological evaluation should always be biological evaluation. The use of newer molecular methods (eg,
implemented as an early diagnostic step (strong, high). gene amplication and sequencing) will likely impact the man-
agement algorithms of immunocompromised patients with
Executive Summary skin and soft tissue lesions and result in the earlier use of path-
Skin and soft tissues are common sites of infection for HIV- ogen-directed antimicrobial therapy [184, 185]. Peripheral
negative patients with a compromised immune system, posing blood biomarkers such as galactomannan and 1,3--D-glucan
a major diagnostic challenge [178, 179], as the differential diag- has been well studied over the past 20 years and has been report-
nosis is broad and includes drug eruption, skin or soft tissue in- ed to be useful in the diagnosis of disseminated fungal infec-
ltration with the underlying malignancy, chemotherapy- or tions by several European investigators. However, sensitivity
radiation-induced skin reactions, graft-vs-host disease among of these tests can be signicantly affected by the use of antifun-
allogeneic transplant recipients, Sweet syndrome, erythema gal drugs, and in the United States their sensitivity has been re-
multiforme, and leukocytoclastic vasculitis [180, 181]. Because ported to be lower than in Europe in various populations of
the intensity and type of immune defect diminishes or alters immunocompromised patients [186].
dermatological ndings, cutaneous lesions that appear localized Empiric antimicrobial therapy should be initiated immedi-
or innocuous may actually be a manifestation of a systemic or ately in these patients on the basis of their underlying disease,
potentially life-threatening infection. The differential diagnosis primary immune defect, morphology of skin lesions, use of
for SSTIs in immunocompromised patients is usually wider prior antimicrobial prophylaxis, allergy history, and inherent
than that for immunocompetent patients and often includes and local proles of antimicrobial resistance. Despite aggressive
bacterial, viral, fungal, and parasitic agents. Organisms that empiric therapy, treatment failure may occur, and the reasons
cause these infections will vary based on the underlying im- for this lack of response include the following: (1) the initial di-
mune defects (eg neutropenia, cellular immune defects, iatro- agnosis and/or treatment chosen is incorrect; (2) the etiologic
genic related to the use of intravascular catheters), and many pathogen is already resistant to the antimicrobial agent; (3) re-
of the infecting organisms are not typically considered sistance develops during treatment; (4) if indicated, surgical
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e39
performed in adult immunocompromised patients, but most initially be clinically subtle in compromised patients, but MRI
clinicians who manage these patients combine blood cultures, scans of the involved area may be helpful in dening the depth
serial antigen detection, nucleic acid amplication techniques, of infections. In such infections, immediate surgical exploration
radiographic imaging, and a biopsy or aspiration of the abnor- by a team experienced in the management of these patients and
mal skin or soft tissue lesion in the hope of increasing the recov- broad-spectrum antibiotic therapy targeted at gram-negative,
ery of the offending pathogen and directing pathogen-specic gram-positive, and anaerobic bacteria are essential.
antimicrobial therapy. Gram-positive pathogens are now the most common bacteri-
This can occur during initial episode fever and neutropenia al organisms isolated from diagnostic cultures obtained from fe-
(rst episode of neutropenic fever that requires systemic antimi- brile neutropenic patients [197, 198]. These pathogens in order
crobial therapy) or during a persisting episode ( persistent of decreasing prevalence include coagulase-negative staphylo-
neutropenic fever unresponsive to broad-spectrum antimicrobi- cocci, viridans streptococci, enterococci, S. aureus, Corynebacte-
al therapy beyond days 47) or during recurrent episodes of rium, Clostridium species, and Bacillus species. SSTIs associated
fever and neutropenia. This determination helps the clinician with these organisms usually begin as a focal area of tender cu-
dene the most likely pathogens and to construct the initial em- taneous erythema, a macular or maculopapular eruption, or a
piric treatment. classic cellulitis. Although rare, they can also cause ecthyma
During the initial episode gram-negative bacteria should be gangrenosumlike lesions that are often confused with spider
primarily targeted by the initial antibiotic regimen because bites, supercial and deep abscesses that become apparent fol-
they are associated with high mortality rates. Although gram- lowing marrow recovery, necrotizing fasciitis, myositis, and my-
positive bacteria are more common, the addition of antibiotics onecrosis. Common infection sites are the groin, axilla, areas of
with gram-positive activity including MRSA is not recommend- cutaneous disruption (eg, vascular catheter or bone marrow as-
ed unless physical ndings suggestive of inammation in the piration sites), or other skin sites that are moist and frequently
skin and soft tissues are present, the patient is hemodynamically abraded. Hematogenous dissemination of gram-positive bacte-
unstable, and risk factors for MRSA are present. For patients rial organisms to the skin and soft tissue is uncommon except
with a persistent episode of fever and neutropenia or recurrent for S. aureus and some Clostridium species. A toxic shocklike
episodes, antibiotic-resistant bacterial or fungal pathogens in- syndrome with associated diffuse erythroderma has been de-
cluding Candida and molds become more common [197199]. scribed with bacteremic toxinproducing streptococci. Painful
Dermatologic manifestations in patients with fever and neu- myositis may also occur with S. aureus infections as a compo-
tropenia include erythematous maculopapular lesions, focal or nent of hematogenous dissemination.
progressive cellulitis, cutaneous nodules, ecthyma gangreno- HSV, varicella zoster virus (VZV), and enteroviruses are rare
sum, and, occasionally, necrotizing fasciitis or myonecrosis causes of cutaneous manifestations in patients with neutropenia
[179, 200]. Ecthyma gangrenosum is a cutaneous vasculitis [202]. Their presence usually reects either a disseminated in-
caused by invasion of the media and adventitia of the vessel fection, or, in the case of HSV, the autoinoculation of virus from
wall by bacteria, which may be visible on histologic stains of bi- mucosal sites to adjacent or distant cutaneous sites. HSV and
opsy specimens. Ecthyma gangrenosum frequently begins as VZV in compromised patients may appear as vesicles similar
painless erythematous papule(s) that often progress and be- to those in normal hosts, or as isolated or multiple benign-look-
come painful and necrotic within 24 hours. These skin lesions ing papules with a central eschar (ecthyma gangrenosumlike
may be discrete or multiple, are found preferentially between lesion). VZV in compromised hosts may present with the tradi-
the umbilicus and the knees, and can increase in size from 1 tional unilateral dermatome distribution, but may also appear as
cm to >10 cm in <24 hours. Ecthyma gangrenosum has classi- discrete or multiple skin lesions in random distribution. Skin
cally been reported to occur with Pseudomonas aeruginosa biopsy is the only reliable method to diagnose cutaneous or dis-
infections, but similar lesions may be caused by other Pseudo- seminated HSV or VZV infection; peripheral blood PCR for
monas species, Aeromonas species, Serratia species, S. aureus, HSV or VZV can be helpful in these patients.
Stenotrophomonas maltophilia, S. pyogenes, fungi including
Candida species, Aspergillus, Mucor, and Fusarium, and even XXIII. What Is the Appropriate Antibiotic Therapy for Patients With
herpes simplex virus (HSV) [201]. SSTIs During the Initial Episode of Fever and Neutropenia?
In contrast to immunocompetent patients, necrotizing fasci- Recommendations
itis and/or myonecrosis are more frequently associated with 63. Hospitalization and empiric antibacterial therapy with
gram-negative or polymicrobial pathogens rather than a single vancomycin plus antipseudomonal antibiotics such as cefe-
gram-positive bacterium. Necrotizing fasciitis can present alone pime, a carbapenem (imipenem-cilastatin or meropenem or
or concurrently with myonecrosis in the patient with fever and doripenem), or piperacillin-tazobactam are recommended
neutropenia. Rapidly progressive necrotizing SSTIs may (strong, high).
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e41
Table 7. Standard Doses of Antimicrobial Agents Active Against Multidrug-Resistant Organisms
Abbreviations: IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus; VRE, vancomycin-resistant enterococci.
(c) Aspergillus SSTIs should be treated with voriconazole against MRSA (eg, vancomycin, linezolid, daptomycin, or cef-
(strong, high), or, alternatively, lipid formulations of ampho- taroline) [209]. Multiple antibiotic-resistant gram-negative
tericin B, posaconazole, or echinocandin for 612 weeks bacilli are more commonly being recovered from cultures of
(strong, low). Mucor/Rhizopus infections should be treated blood and soft tissues, and antibiotic modication is necessary
with lipid formulation amphotericin B (strong, moderate) or when their presence is suspected or documented (Table 7)
posaconazole (strong, low) (Table 6). The addition of an echi- [204]. Treatment of yeast and mold infections should follow
nocandin could be considered based on synergy in murine IDSA and NCCN guideline recommendations [187, 189].
models of mucormycosis and observational clinical data Although skin and soft tissues are less frequent sites of infec-
(weak, low). tion in patients with persisting or recurrent fever and neutropenia
(d) Fusarium species infections should be treated with (<10%), they often represent a site of infection dissemina-
high-dose IV voriconazole or posaconazole (strong, low). tion. Among the responsible pathogens, 10%15% are caused
(e) Begin treatment for antibiotic-resistant bacterial organ- by antibiotic-resistant gram-negative bacilli; 30%40% by anti-
isms, in patients currently on antibiotics (strong, moderate). biotic-resistant gram-positive organisms (coagulase-negative
(f ) Intravenous acyclovir should be added to the patients staphylococci, MRSA, and vancomycin-resistant enterococci),
antimicrobial regimen for suspected or conrmed cutaneous but most (>50%) are caused by yeast or molds [198, 210,
or disseminated HSV or VZV infections (strong, moderate). 211]. In 2012, infections caused by yeast and molds were the
70. Blood cultures should be obtained, and skin lesions in this major cause of associated morbidity and mortality in patients
population of patients should be aggressively evaluated by culture with prolonged and profound neutropenia [198, 210]. Diagnosis
aspiration, biopsy, or surgical excision as they may be caused by of fungal infections remains difcult, and benets from fungal
resistant microbes, yeast, or molds (strong, moderate). antigen or DNA detection remain inconsistent [212, 213]. How-
71. The sensitivity of a single serum fungal antigen test (1,3- ever, recovery of fungi from aspiration or biopsy of skin or deep
-D-glucan or galactomannan tests) is low particularly in soft tissues warrants aggressive systemic antifungal therapy.
patients receiving antifungal agents, and benets from laborato- Surgical treatment should be also considered in patients with
ry tests for fungal antigen or DNA detection remain inconsis- skin and soft tissue changes caused by angioinvasive molds
tent (strong, moderate). (eg, Mucor, Rhizopus, and Aspergillus).
72. PCR in peripheral blood for HSV and VZV might be The incidence of invasive candidiasis prior to the routine use
helpful in establishing a diagnosis of disseminated infection in of azole antifungal prophylaxis was 12% in patients with pro-
patients with unexplained skin lesions (weak, moderate). found and prolonged neutropenia [214]. Candida albicans
is the most frequently isolated species; however, uconazole-
Evidence Summary resistant yeast (ie, Candida krusei and Candida glabrata) are
In patients with persistent unexplained fever of their rst epi- increasingly common due to the widespread use of azole prophy-
sode (after 47 days) or recurrent fever, yeast and molds are laxis [214]. Supercial cutaneous candidiasis presents as intertri-
the major cause of infection-related morbidity and mortality go, vaginitis, balanitis, perleche, and paronychia [215] and rarely
(Table 7) [187, 189, 203]. These later infections are most com- causes dissemination. However, up to 13% of patients with inva-
mon among high-risk patients with prolonged and profound sive disseminated candidiasis develop single or multiple nodular
neutropenia and they should be considered in any patient skin lesions [216, 217]. These lesions can appear as discrete pink
with neutropenia and skin and soft tissue lesions suggestive of to red papules (0.51.0 cm) and are usually found on the trunk
infection. In addition, MRSA should also be considered if and extremities [215, 217]. Candida skin lesions are usually non-
patients are not receiving antimicrobial agents with activity tender, but may develop central pallor, or become hemorrhagic if
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e43
Nocardia documented cryptococcal meningitis by several weeks. Cutane-
Cutaneous Nocardia infections usually represent metastatic foci ous cryptococcal infections may appear as papules (often simi-
of infection that have originated from a primary pulmonary lar to molluscum contagiosum lesions), nodules, pustules,
source [230]. Nocardia farcinica, Nocardia brasiliensis, and chronic draining necrotic ulcers, or, more subtly, as cellulitis
other Nocardia species have been associated with cutaneous dis- [235]. Cryptococcal cellulitis has occurred in recipients of
ease. The dermatologic manifestations are usually limited to blood, bone marrow, or SOT, although the incidence has dra-
subcutaneous nodules or abscesses and panniculitis. Soft tissue matically decreased with the prophylactic use of the newer
abscesses are frequently painless and are described as being cold azole agents, particularly uconazole. Fluconazole is often
to the touch. The incidence of local and disseminated Nocardia used as initial treatment, for patients with mild infections, or
infections has decreased with the routine use of SMX-TMP to complete treatment after the patient has shown clinical and
prophylaxis for patients who experience prolonged periods of microbiologic improvement with amphotericin B and 5-ucy-
cellular immune deciency. SMX-TMP remains the treatment tosine induction therapy [236]. Surgical debridement and/or
of choice, but other sulfa antibiotics (eg, sulfadiazine and sulfa- drainage are not helpful in the management of skin or soft tis-
soxazole), amikacin, imipenem, meropenem, third-generation sue cryptococcal infections.
cephalosporins (ceftriaxone and cefotaxime), minocycline, ex- Cutaneous manifestations of acute progressive disseminated
tended-spectrum uoroquinolones (eg, moxioxacin), linezol- histoplasmosis are rare and usually occur in patients with severe
id, and dapsone are effective in vitro and in animal models cellular immune deciency [237, 238]. Skin lesions appear as
(Table 6). Combination therapy with other agents should be nonspecic maculopapular eruptions that become hemorrhag-
considered in patients with severe infections or profound and ic, but oral or cutaneous ulcers are sometimes present, particu-
lasting immunodeciency. Prolonged therapy is important, larly in the subacute, disseminated form of the disease.
and the duration of treatment (624 months) should take Histopathologic analysis of these skin lesions reveals necrosis
into account the presence of disseminated disease and the ex- surrounding the supercial dermal vessels, and with special
tent of the patients underlying immunosuppression. Surgical stains, both intracellular and extracellular yeast may be seen.
debridement is recommended for necrotic nodules or large sub- Prompt administration of amphotericin B therapy is the recom-
cutaneous abscesses. mended treatment for patients with cellular immune deciency
and acute, life-threatening, progressive disseminated histoplas-
Fungi mosis. Patients often show a rapid clinical improvement within
Cutaneous mold infections have been increasingly reported in 12 weeks, and itraconazole can then replace amphotericin B to
immunocompromised patients with primarily cellular immu- complete at least 612 months of treatment [237]. Patients with
nodeciency. Skin lesions can occur as a manifestation of a dis- illnesses that result in profound and prolonged immune sup-
seminated disease, a primary cutaneous inoculation, or in the pression should receive long-term suppressive therapy with itra-
skin site of a previous IV line [221, 230]. The most common conazole after the initial treatment course is complete.
molds causing cutaneous manifestations in these patients in-
clude Aspergillus, Mucormycosis, Scedosporium, and Fusarium Viruses
species [231234]. Skin lesions can present as papules, nodules, VZV is one of the 2 most frequent herpesviruses to cause cuta-
or ulcers, or with the dermatological appearance of ecthyma neous infection in immunosuppressed patients [239]. Patients
gangrenosum. Skin biopsy should be performed for diagnostic without a preceding history of VZV exposure are at signicant
purposes and resection of the entire lesion or debulking pro- risk of developing severe chickenpox if exposed, but herpes zos-
cedures should be considered in cases where there is either a ter (also known as shingles) with or without dissemination is a
single lesion or localized disease is present. In instances of As- more frequent clinical concern. Between 65% and 70% of adult
pergillus species, Scedosporium apiospermum, and Fusarium patients are seropositive for VZV, and this identies those pa-
species infections, voriconazole is the best therapeutic option. tients at risk for future reactivation infection. Herpes zoster oc-
Amphotericin B is an excellent alternative. Posaconazole is curs most frequently during the rst year following
also a reasonable alternative in combination with amphotericin chemotherapy treatment, or following receipt of an HSCT or
B or as a transition to oral therapy (Table 7). a SOT. Depending on the intensity of treatment or type of trans-
Cryptococcal infections originate in the lungs, often with plant, 25%45% of such patients develop dermatomal zoster,
early hematogenous dissemination to the meninges and skin with a 10%20% risk of developing dissemination without
or soft tissues, but primary cutaneous cryptococcosis also oc- prompt and effective antiviral therapy. A few patients present
curs [235]. Single or multiple painless skin lesions involving initially with disseminated cutaneous infection that may
the face and scalp develop in 5%10% of clinically infected pa- mimic atypical varicella, but some patients may present with
tients, and in some patients, these lesions may precede nonspecic lesions that do not initially have the vesicular
IDSA Practice Guidelines for SSTIs CID 2014:59 (15 July) e45
inclusion criteria, is necessary for enrollment in the clinical for honoraria from Bayer, Merck, Wyeth-Ayerst, AstraZeneca, Pzer,
Ortho-McNeil, Cubist, Vicuron, InterMune, Peninsula, Johnson & Johnson,
trial.
Cepheid, Replidyne, Kimberley-Clark, Targanta, Schering-Plough, Enturia,
The priorities for further research are as follows: Optimer Pharmaceuticals, Cadence, Implicit, Cardinal, Durata, 3M, Applied
Medical, and BD-GeneOhm; and has received a clinical trial grant from
1. Rapid and specic diagnostic assays are needed for iden-
Tetraphase. E. J. C. G. has served as a consultant to Schering-Plough, Vir-
tication of microbes that cause cellulitis. aPharm, Replidyne, Occulus Innovative Sciences, Theravance, Cerexa,
2. Inexpensive agents are needed that are effective against Merck, and Optimer Pharmaceuticals; has received honoraria from
Merck, Johnson & Johnson; and has received research grants from Repli-
groups A, B, C, and G streptococci as well as staphylococci in-
dyne, Occulus Innovative Sciences, Cubist, Theravance, Pzer, Cerexa,
cluding MRSA. Johnson & Johnson, Merck, and Optimer Pharmaceuticals. S. L. G. has re-
3. Investigations are needed to determine the pathogenesis of ceived stocks/bonds from Optimer Pharmaceuticals, Cubist Pharmaceuti-
soft tissue infections caused by streptococci. This should in- cals, and Cempra Pharmaceuticals has received honoraria from IDSA
(Editor, Clinical Infectious Diseases); has served as a consultant to Cempra
clude the respective roles of toxins and host response molecules Pharmaceuticals; and has received grants from the National Institutes of
in the genesis of redness, swelling, pain, and edema. Health. S. L. K. has served as a consultant to Novartis, Pzer, and Wyeth;
4. Clinical trials should be performed that include patients has been a site PI for Cubist, Cerexa, and Optimer; and has received hono-
raria from UpToDate and Merck. All other authors report no potential
with severe soft tissue infections (eg, necrotizing fasciitis and
conicts.
gas gangrene) and immunocompromised patients. The lack of All authors have submitted the ICMJE Form for Disclosure of Potential
evidence-based approaches results in clinical decisions being Conicts of Interest. Conicts that the editors consider relevant to the con-
tent of the manuscript have been disclosed.
made based on physicians best opinion, or extrapolation
from other patient populations.
5. Investigations should determine host and pathogen fac- References
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